Quite frequently, patients are treated with regard to their fluid balance. Likewise, such a treatment may be directed to the removal of fluid or to the replacement or addition of fluid. The present invention aims at providing a method and devices applicable in the field or context of fluid balance or fluid status.
By means of the present invention a method for assessing a patient's sensitivity to fluid removal from the patient's vascular system—or to fluid replacement or fluid addition—with regard to the patient's hydration state is suggested. Also, a controller for carrying out the method according to the present invention is provided, as well as an apparatus, a device comprising the present invention, a controller, a digital storage means, a computer program product, and a computer.
The method according to the present invention is defined by the feature combination of claim 1. Accordingly, in one aspect of the present invention, an assessment is suggested comprising the step of determining a value reflecting the distribution of a fluid between at least two distribution spaces (also referred to as a first and a second distribution space below) of the body of the patient, or reflecting changes of the value or reflecting changes of one or more of the distribution spaces. It further comprises assessing whether the value fulfils at least one criterion.
The patient can be either a human being or an animal. The patient may be sound or ill. The patient may be in need of medical care or not. The patient may be a dialysis patient or not.
In another aspect of the present invention, the controller is intended or provided or used or configured to carry out the method according to the present invention.
In yet another aspect of the present invention, an apparatus is provided, the apparatus comprising means for obtaining a value reflecting or concerning the distribution of a fluid between at least a first and a second distribution space of the patient, and at least one controller according to the present invention.
In another aspect of the present invention, the digital storage means, in particular a disc, CD or DVD, has electrically readable control signals which are able to interact with a programmable computer system such that the method according to the present invention will be executed.
In another aspect of the present invention, the computer program product has a program code stored on a machine readable data medium for executing the method according to the present invention when executing the program product on a computer.
In another aspect of the present invention, the computer program has a program code for the execution of a method according to the present invention when executing the program on a computer.
Embodiments can include one or more of the following features.
In certain embodiments, the value reflecting the distribution or changes thereof is determined from one or more measured or calculated values and/or figures and/or terms, the measured or calculated value(s), figure(s), and term(s) being different from the value to be determined.
In some embodiments, the measured or calculated values and/or figures and/or terms are gained in the presence of the patient.
In certain embodiments, the measured or calculated values and/or figures and/or terms are gained in the absence of the patient (that is, without the patient being present). For example, the measured or calculated values and/or figures and/or terms may be already at hand when carrying out the method according to the present invention. For example, in some embodiments, the measured or calculated values and/or figures and/or terms were collected in advance of carrying out the method according to the present invention.
In some embodiments, the fluid is a body fluid such as blood or water comprised within the body, e.g. extracellular water. In certain embodiments, the fluid is one fluid, in particular one body fluid.
In certain embodiments, the fluid is incorporated or is intended to be incorporated, e.g. as drinking water, as replacement fluid as it is known in the art, etc.
In some embodiments, the first or the second distribution space is defined as the blood volume.
In certain embodiments, the second distribution space is the extracellular fluid volume.
In some embodiments, the second distribution space are the interstices, the interstitium, or the interstitial volume, respectively.
In some embodiments, the method further includes determining a saturation degree of at least one of the distribution spaces and using said saturation degree as value or as criterion.
In certain embodiments, the saturation degree is determined by means of a curve. The saturation degree can be a numerical parameter, a “0/1” information, or any other type of information that indicates the saturation, e.g., the slope of a curve indicating the distribution of the fluid at issue between two or more distributions spaces, or what is defined or approximated as saturation by the skilled one.
In some embodiments, the saturation degree is a ratio between the sizes of two distribution spaces, or a ratio between changes of two distribution spaces over time, and the like.
In certain embodiments, the saturation degree indicates, what percentage or part of additional fluid will be incorporated by a first distribution space and what percentage or part will be incorporated by one or more distribution space different from the first distribution space.
In certain embodiments, the method further includes determining a saturation degree based on the Guyton curve—with the Guyton curve being a curve depicting the blood volume BV over the extracellular fluid volume ECW of a patient explaining physiologic interdependencies between extracorporeal water (ECW) and the blood volume—or an adaption thereof to human beings or particulars.
In some embodiments, the method further includes calculating a correlation between changes in weight—particular pre-weight, i.e., a dialysis patient's weight at the beginning of another dialysis treatment, respectively—over at least two measurements and values representing an anemia state of the patient or changes thereof at those measurements. The patient can be a dialysis patient.
In certain embodiments, the anemia state of the patient is defined by means of direct or indirect measurements or calculations of the mass, the concentration or the volume of a substance, e.g. hemoglobin (Hb), or changes thereof.
In some embodiments, the anemia state of the patient is defined by means of direct or indirect measurements or calculations of the haematocrit (Hct) or changes thereof.
In certain embodiments, the method further includes comparing the calculated correlation with a threshold or a range.
In some embodiments, the threshold or range is predetermined or pre-set.
In certain embodiments, the threshold is the slope or inclination of a curve in a graphical illustration.
In some embodiments, the range is a combination of—more than one—thresholds.
In certain embodiments, the result of the assessment may be the finding that the value falls or does not fall within a range. For example, the result may be that the value is above or below a threshold.
In some embodiments, the method further includes assessing the size of at least one distribution space based on measured values and/or results of calculations reflecting a hemoglobin (Hb) state. The hemoglobin (Hb) state may be reflected by the Hb concentration, its total mass, its volume, change thereof over time, respectively, etc.
In certain embodiments, the method further includes assessing the size of at least one distribution space based on measured values and/or results of calculations reflecting the haematocrit (Hct) or changes thereof over time.
As is evident to the skilled person, the present invention is not limited to the assessment of the size of at least one distribution space based on measured values and/or results of calculations reflecting a hemoglobin (Hb) state or the haematocrit (Hct) or changes thereof. The present invention can of course also be carried out based on measured values and/or results of calculations reflecting a mass, concentration or volume (and changes thereof) of any other suitable substance or marker.
In some embodiments, the method further includes using the size of at least one distribution space as was obtained based on results from measurement of blood samples and/or from blood comprised in extracorporeal blood lines by means of an appropriate monitor. The measurements can be made—or were made or terminated before carrying out the method according to the present invention—by measuring the optical properties of the blood by optical sensors and/or by assessing acoustic properties like transit times and/or propagations velocities of ultrasonic pulses by ultrasonic sensors.
Also, in certain embodiments any samples used for measurements were obtained before carrying out the method according to the present invention.
For determining the hydration state also any appropriate monitor can be used, such as monitors based on bioimpedance or dilution techniques.
In certain embodiments, the method further includes using the size of at least one distribution space as obtained based on results from urine samples.
In some embodiments, the method further includes using the size of at least one distribution space as obtained based on results from tissue samples.
In certain embodiments, the method further includes using the size of at least one distribution space as obtained based on results obtained from measuring a concentration, mass, volume or changes thereof of a substance being comprised by the group comprising at least any substance produced naturally in the body of the patient, in particular hemoglobin, albumin, insulin, glucose, C-reactive protein (CRP), and non-endogeneous substances, in particular pharmaceutically effective substances.
In some embodiments, the method further includes assessing pre-dialysis values of the patient.
In certain embodiments, the pre-dialysis values represent the patient's condition(s) seconds or minutes (up to, e.g., a half-hour, one hour, two hours or the like) before starting the next dialysis treatment.
In some embodiments, the method further includes assessing post-dialysis values of the patient.
In certain embodiments, the post-dialysis values represent the patient's condition(s) seconds or minutes (up to, e.g., a half-hour, one hour, two hours or the like) after finishing the next dialysis treatment.
In certain embodiments, the method further includes plotting results of the assessment for visual assessment.
In some embodiments, the at least one criterion is, or comprises, at least one threshold or at least one range.
In certain embodiments, the at least one criterion is pre-set or predetermined.
In some embodiments, the at least one criterion is variable.
In certain embodiments, the method further includes determining the criterion.
In some embodiments, the method further includes the step of calculating and/or measuring parameters reflecting the volume of at least one of the distribution spaces of the patient or an approximation thereof.
In certain embodiments, the method further includes determining or adjusting a dosage of a medicament to be administered to a patient for improving the patient's anemia state based on the obtained relation between the calculated or measured value(s) and the criterion.
In some embodiments, the controller comprises means for obtaining information concerning the distribution or the distribution space(s). In certain embodiments, the means may be a monitor for obtaining information concerning the distribution, an input means for inputting information concerning the distribution or the distribution space(s), or the like.
In certain embodiments, the apparatus is or comprises a monitor for obtaining information concerning the distribution.
In some embodiments, the monitor for obtaining data related to the distribution and/or for obtaining data reflecting the relation between the sizes or the volumes of at least two distribution spaces is a monitor as described in WO 2006/002685 A1. The respective disclosure of WO 2006/002685 A1 is hereby incorporated in the present application by way of reference. Of course, the present invention must not be understood to be limited to monitors obtaining data by bioimpedance measurements as is described in WO 2006/002685 A1. Other bioimpedance methods known in the art and also any other methods known in the art such as dilution measurements and also any other method known to the skilled person are also contemplated and encompassed by the present invention as well.
In certain embodiments, the apparatus comprises a monitor for measuring Hb concentrations (e.g., in [g/dl]) and/or for determining the blood volume by means of any monitor as described in “Replacement of Renal Function by Dialysis” by Drukker, Parson and Maher, Kluwer Academic Publisher, 5th edition, 2004, Dordrecht, The Netherlands, on pages 397 to 401 (“Hemodialysis Machines and Monitors”), the respective disclosure of which is hereby incorporated by way of reference.
In some embodiments, the monitor is configured to measure the blood volume and/or the concentration of the substance—in particular Hb—by means of measuring an electrical conductivity.
In certain embodiments, the monitor is configured to measure the blood volume and/or the concentration of the substance—in particular Hb—by means of measuring an optical density.
In some embodiments, the monitor is configured to measure the blood volume and/or the concentration of the substance—in particular Hb—by means of measuring a viscosity.
In certain embodiments, the monitor is configured to measure the blood volume and/or the concentration of the substance—in particular Hb—by means of measuring a density.
In some embodiments, the monitor comprises one or more corresponding probes and/or one or more sensors for carrying out the measurements such as electrical conductivity sensors, optical sensors, viscosity sensors, density sensors, and the like.
In certain embodiments, the apparatus furthermore comprises an output device for outputting results provided by the controller.
In some embodiments, the output device is a monitor having a display, a plotter, a printer or any other means for providing an output.
In certain embodiments, the output device is connected to an actuator for controlling administration of a substance to the patient.
In certain embodiments, the device may be used for treating a patient by means of dialysis.
In other embodiments, the device may be used for treating a patient (or the patient's blood) by hemofiltration, ultrafiltration, hemodialysis, etc.
The embodiments may provide one or more of the following advantages.
In some embodiments, the present invention provides information on the question into what body compartment or distribution space a fluid, e.g. drinking water or a replacement fluid, goes to when ingested by the patient. In particular, by means of certain embodiments of the present invention, a distinction can be made whether ingested fluids increase, for example, the blood volume or the interstices or both. This distinction may help to understand the patient's sensitivity to fluid removal. It may contribute to a more thorough understanding of cardiovascular circumstances and conditions, in particular cardiovascular stress. In some embodiments, this distinction can be readily made on basis of the measured or calculated values reflecting increases of, for example, weight and Hb.
In certain embodiments, by means of the present invention it can be found out whether the administration of volume (i.e., a fluid) to the patient—e.g, by means of replacement solutions such as HAES® and the like—can be of advantage to the patient. This is particularly possible in cases where the concentration, or mass, or volume of a substance at issue—such as hemoglobin—is constant over time or can be approximated to be so.
In some embodiments, by means of the present invention it can be determined whether an on-going replacement of volume by means of solutions such as HAES® or addition of fluid is better stopped.
Further, dialysis patients with accumulated extravascular fluid—as it is the case with anasarca or edema—can also benefit from certain embodiments of the present invention: Fluid which increases the volume of such an accumulated extravascular fluid can be identified by means of the method according to the present invention. Consequently, such a patient will be correctly considered as overhydrated—even if, e.g., the patient's reaction during ultrafiltration indicates a dry state. Accordingly, the dialysis, e.g. the ultrafiltration rate or duration, may be adapted to the actual need of the patient. The same advantage may apply upon adoption or administration of diuretics which is also contemplated by the present invention. This advantage is not limited to dialysis patients.
Other aspects, features, and advantages will be apparent from the description, figures, and claims.